Fig. 1. Schematic diagram of virus detection based on SERS technology

Fig. 2. SERS sensors and platforms are designed in a variety of diverse ways for label-free detection of SARS-CoV-2. (a) Schematic diagram of the design and operation process of the COVID-19 SERS sensor^[36]; (b) flexible substrate combined with SERS metal-insulator-metal nanostructures and machine learning-based label-free detection platform^[42]; (c) schematic diagram of SnS₂ microsphere substrates design^[44]; (d) Raman enhancement mechanism of Cu₂O nanoarray with significant enhancement factor^[45]

Fig. 3. Machine learning techniques are applied to SARS-CoV-2 label-free detection. (a) Identification of pure S protein standard samples by SERS spectroscopy using PCA^[47]; (b) SERS biosensors are engineered with 3D porous Ag nanoparticle-based microplasma-engineered nanoassemblies (denoted as AgMEN) deposited on cellulose paper (left) and functionalized with antibodies (AgMEN@Ab)(center part) to detect the corresponding antigens by analyzing the SERS response (right)^[48]

Fig. 4. Application of SERS nanoprobes in label detection and differentiation of SARS-CoV-2. （a) Schematic of the SERS assay based on one-step aptamer recognition for rapid point-of-care detection of SARS-CoV-2 virus within 5 min^[51]; (b) stepwise reactions of RBD probe for SARS-CoV-2 capture and detection with SERS nanotags, for virus and variant identification based on the average Raman spectrum results^[54]

Fig. 5. Application of SERS label detection method for the detection of RNA and proteins from SARS-CoV-2 virus lysates.(a) Schematic illustrations of the preparation of SERS tags and the signal amplification strategy for SERS detection of SARS-CoV-2 RNA^[55]; (b) preparation of Au@4MBN@Ag NPs and fabrication of two-dimensional SERS sensing chip for SARS-CoV-2 RNA detection^[56]; (c) schematic illustration of the quantitative evaluation of SARS-CoV-2 using the SERS-based aptasensor^[57]

Fig. 6. Multi-mode virus detection scheme incorporating SERS technology. (a) Schematic of the triple-mode biosensors for COVID-19 virus RNA detection^[59]; (b) PCR amplification process for bridge DNAs and SERS detections for bridge DNAs^[60]

Fig. 7. SERS labeling method applied to the detection of influenza A virus. (a) Schematic diagram of using SERS assisted with pre-filtering to sensitively detect influenza A virus ^[64]; (b)schematic of the IMBSIs@Ag-SERS method for H5N1 influenza virus detection^[65]

Fig. 8. SERS labeling method applied to the detection and differentiation of multiple respiratory viruses. (a) Working principle of dual aptamer-immobilized Au nanopopcorn substrate for virus assays^[69]; (b) collection of throat swab sample and operating procedure for the simultaneous quantitative detection of three respiratory viruses via the Fe₃O₄@Au-based SERS LFA strip^[70]

Fig. 9. SERS technology applied to the detection of human immunodeficiency virus (HIV-1) and norovirus (NoV). (a) Schematic diagram demonstrating rapid handheld SERS platform for HIV detection^[73]; (b) the stepwise dual-modality NoV detection^[77]

Fig. 10. SERS technology applied to the detection of dengue virus (DENV). (a) Schematic of platform for DENV2 NS1 detection in a single infected mosquito sample with the integration of nanoyeast scFvs affinity probes and nanobox-based SERS nanotags^[83]; (b) schematic illustration of SERS assay of DENV gene via a cascade enzyme-free signal amplification strategy of LCHA and HCR^[84]

Fig. 11. SERS technology used for the detection of DNA viruses such as hepatitis B virus(HBV) and monkeypox virus(MPXV).(a) Schematic illustration showing the integration of a microfluidic device with the SERS-active substrate based on Au-Ag coated GaN surface^[92]; (b) schematic diagram of CRISPR/Cas12a-SERS principle analysis^[93]; (c) the principle of MPXV detection by colorimetric-SERS dual-mode ICA^[97]

Fig. 12. CRISPR/Cas-SERS platform applied to the detection of viral genetic material. (a) Schematic diagram of the gene detection by using the CRISPR/dCas9-based SERS method, assisted with HRP-Catalyzed signal amplification^[111]; (b) schematic diagram of the proposed CRISPR/Cas12a-SERS platform for amplification-free ASFV dsDNA detection^[112]

Fig. 13. Portable Raman spectrometer devices applied to SERS virus detection schemes. (a) Schematic illustration of SERS based immunoassay platform(with a portable Raman spectrometer)^[115]; (b) schematic diagram of the detection of influenza A virus H1N1 by SERS and gold electrodeposition nanostructure^[116]; (c) schematic diagram of a SERS detection method based on one-step aptamer identification using a portable Raman spectrometer for rapid and point-of-care detection of SARS-CoV-2 virus in less than 5 minutes^[51]